DESCRIPTION (Applicant's abstract):Patients with spinal cord injury frequently suffer from respiratory complications due to their inability to cough and clear secretions. In recent animal studies, we have demonstrated that lower thoracic spinal cord stimulation (SCS) and magnetic stimulation (MS) results in the generation of large increases in airway pressure and high peak flow rates. These techniques, therefore, have the potential to produce an effective cough mechanism in spinal cord injured patients. The purpose of these studies is to resolve important basic science issues concerning these techniques in animal studies. In OBJECTIVE I, the efficacy of cough by these techniques will be assessed by radiolabeled clearance studies. In OBJECTIVE II, the pathway(s) by which the motor nerves innervating the expiratory muscles are activated during SCS and MS will be determined. The importance of motor root activation via stimulation of spinal cord pathways will be assessed by monitoring pressure generation before and after sequential section of the ventral roots. The specific pathways responsible for pressure generation will be localized anatomically by evaluating the effects of spinal cord section. Nerve compound action potentials will also be recorded from the motor roots during stimulation. In OBJECTIVE III, the electric field generated around and within the spinal cord during SCS and MS will be measured and used in conjunction with finite element analysis modeling techniques to determine optimum electrode and coil design. In OBJECTIVE IV, we will characterize the changes in expiratory muscle structure and function following upper motoneuron denervation. An effective cough is dependent upon optimal function of the expiratory muscles which are most likely atrophied in patients with spinal cord injury. Therefore, we will also assess the capacity or SCS and MS to maintain expiratory muscle function in a chronic animal model of spinal cord injury. In OBJECTIVE V, the safety profile of SCS will be assessed in chronic animals. The results of these studies should provide important information relevant to the potential use of these techniques in human clinical trials. Restoration of affective cough mechanism may allow patients with spinal cord injury to clear secretions more easily, reduce the incidence of respiratory complication and, ultimately, improve their life quality.